recognizes the importance of NHS to better understand the disease and as a baseline to determine efficacy and obtain regulatory approval of new therapies.

calls for the NHS study team to be well-informed about MLD and to give back to the participants ideas and insight into improving the participants quality of life and ongoing clinical care.

calls for study sponsors to collaborate pre-clinically up front with other researchers and industry to design a study that meets the sponsor’s needs as well as reasonably anticipated future needs

calls for study data to be open and accessible as raw data (in its entirety) to future researchers. The Manifesto recognizes that some limited time protection may be necessary to honor publishing and IP rights.

At the DC meeting there was extensive discussion and sharing of perspectives and concerns about openNHS from many points of view.

We are pleased to report the meeting was a success on all fronts! MLD Foundation, on behalf of those affected with MLD and the ongoing research community, was able to facilitate full support of the Manifesto and will be working with MLD collaborators in general, as well as Shire as sponsor of the current US late infantile NHS, to implement the Manifesto on current and future MLD Natural History Studies.

We look forward to sharing more specifics about what this means to MLD families and NHS study participants in the near future.

We will also be sharing our success with other advocacy groups with the hope that they too can call for openNHS in their communities.

Great Patient Focused Drug Development (PFDD) meeting at the FDA Tuesday discussing patients perspective on the neurological inborn errors of metabolism (IEM). Dean Suhr, president of the MLD Foundation, spoke on the second panel of the day and was able to both share and stir the pot a bit with regard to some of the patient perspectives on what we want in therapies, risk/benefit, access to trials in the US, compassionate/named access, patient reported outcomes, and consent. It’s not all about statistics and biochemistry – we have life to live!

View from the panel of ½ of the audience of advocates, families, researchers, and industry at the FDA PFDD meeting on IEM.

Also met the Medical Officer at the FDA assigned to gene therapy and made sure she talked to Becky Vivian, a MLD mom who was there with her kids Eli and Ella showing the remarkable results from the Italian gene therapy clinical trial.

The Vivian family – both kids had the Italian Gene Therapy and are on no post-transplant drugs. They, and the rest of the trial participants, are doing great.

In the next couple of days we’ll be sharing how to add your voice to the formal written docket for this meeting. This is our opportunity for the MLD community to be heard so we hope for many of you to share.

A MLD grandmother was also present – we had a great talk. Turns out she is a researcher and has done some work at the NIH. She wants to work with us … and you … to write a paper on bone marrow transplant outcomes. We’ll have more to share on that soon too.

A new Natural History Study (NHS) for MLD was launched a few weeks ago. We have taken the bold step of recommending that families NOT participate in this study … for now:

It is our belief that all natural history studies be OPEN access, meaning the study data be maximized by being made available to other researchers from other academic institutions and companies, and be as collaborative as possible. Properly designed studies will protect your privacy while maximizing the use of your data to facilitate longevity in MLD research.

In our opinion this new NHS does not adequately meet this criteria. We are (February 2014) in discussions with the study sponsors to address these concerns.

This study is the fourth NHS that we are aware of for MLD and was launched by a long-standing pharmaceutical partner and MLD collaborator, Shire. We want to be clear that our don’t participate for now recommendation is not a Shire specific issue nor is Shire resisting discussing our concerns. Further, this “not participate” stance is not because there are any fundamental scientific problems with the study, rather it’s that we want to optimize the value, usefulness, and knowledge gained from this rare disease Natural History Study for the researchersand for the patients.

We are actively working to bring the MLD community of Shire, GSK, Biomarin, several academic institutions, several other advocacy groups, and even some local treating clinicians together in the next month or two to collaboratively work on the following concerns and requests so we can get back to helping recruit for this study.

We are asking for two things before we encourage families to participate in this, or any other Natural History Study …

OPEN collaborative Natural History Studies … meaning that the study is designed collaboratively and all ofthe the collected RAW data is made available openly to all future researchers.

MLD natural history studies are invasive and painful for the child who participates (nerve conduction and Lumbar Puncture/Spinal Taps). They also require a commitment that significant time and energy be put forth by families to make the repeat their visits to the study center knowing that they will not be receiving any therapy clinical trial access, i.e. they are giving to hopefully help the next generation of patients, not their own children.

Today, the current practice is one company designs their own NHS, collects and silos the raw data, uses the data for their application with the FDA, and then publishes the highlights. Since only the summary data is published, the next company has to start from scratch with their own new study, engaging & testing more patients, etc. That requires twice as many patients, twice as much patient sacrifice, twice as much cost, and perhaps twice as much time. We don’t have a large enough community or enough time to double and triple dip – in fact, yesterday we lost another MLD patient, the 9th we know of this year.

The results from natural history studies are necessary for a new FDA/EMA therapy approval applications,however, these patients are untreated so their data is independent of any particular therapy. Hence a NHS, just like developing a newborn screen, is a matter of common concern, not competitive advantage.

We are asking that Natural History Studies be collaboratively designed, collaboratively implemented, and all RAW data (not just the published summaries) be available for any researcher to access for any future study. This collaborative approach will likely involve cost sharing as well so it’s complicated to set up but this approach allows us to gather the data as efficiently and as quickly as possible – while optimizing the “use” of the patient community.

Give back to the patients/families with each NHS study visit … give the families information to take home after each visit to help them improve quality of life for their loved ones.

The NHS study centers have experts in gathering the NHS data, however, while they may understand lysosomal disease or leukodystrophies in general, they are generally not currently providing any direct MLD clinical feedback to the patients.

We already have a model for this in our community, the NDRD in Pittsburgh. In fact, families visit and re-visit the NDRD from literally across the country for the clinical expertise and are then recruited into the natural history studies. The NDRD has become a source of expertise and clinical support for many similar rare diseases. They give clinical recommendations to the family to improve day to day quality of life and also become a medical resource for the local treating care team in the family’s home town.

We are asking that each study center be equipped to be a Center of Excellence for MLD where they can, and do, provide clinical expertise with each visit in addition to gathering the specific NHS data. This approach, as has been demonstrated by the NDRD, is a model that works for research and the families.

We are working to develop a Standard of Care for MLD to further support these clinical Center of Excellence goals and the local treating physicians when they go back home.

To our knowledge, no patients have been recruited for this specific Natural History Study. We hope to impact the collaborative and clinical nature of how the study proceeds before any patients are enrolled, and frankly do not think these requests will impact the core study design in any significant ways. As we all know, once patients are enrolled and data gathering momentum is established, change becomes more difficult.

We have excellent contact and influence with the MLD families worldwide. We are using this position and those relationships to try to affect a fundamental change in how Natural History Studies are implemented for MLD and for all rare diseases.

It is very bold to take this sort of position publicly – but it’s our moral responsibility to stand up for the patients. We firmly believe this “patient-first” while “optimizing research” stance is optimal for patients and researchers.

If your organization supports this philosophy for OPEN Natural History Studies please comment here and then email us to let us know. Advocacy groups can be the catalyst for these changes.

Until this morning, I didn’t even know what paroxysmal nocturnal haemoglobinuria (Marchiafava-Micheli syndrome or PNH) was – all I need to know was they are fellow brothers and sisters with rare disease. We must come to their support.

Enough already! Well over 95% of the rare diseases are struggling to understand their disease and develop therapies … yet here we have a disease with a therapy that some bean counting bureaucrat says $$ x number of patients = too much. What they conveniently ignore in their public stance is that Alexion, like all rare disease drug companies, will work with countries that need help to offset the list price because they care about the patient. PHARMAC (New Zealand’s purchasing agency) you should care too!

We must not allow any more piecemeal incursions on the progress we are making towards therapies for all rare diseases. If your disease is lucky enough to have a therapy in the future – the PNH struggle could be yours. We must education and inform now!

An acceptable treatment protocol in place that changes the outcome for patients diagnosed early with the disease

An understanding of the condition’s natural history

An understanding about who will be treated as a patient

A NBS screening test that is reliable for both affected and unaffected patients and is acceptable to the public.

We are slowly becoming better at identifying and diagnosing Rare Diseases, unfortunately diagnosis occurs most often after symptoms are presenting. The great majority of the 7,000+ rare diseases do not have efficacious therapies. More than half of all rare diseases affect children and 30% of those children will not live to see their 5th birthday (1).

“There is always a therapy – it may not be a cure or a disease specific treatment, but we can always do something to optimize quality of life.” Paraphrase of Dr. Marc Patterson from the Mayo Clinic, Rochester MN.

With MLD and many other rare diseases, the diagnostic odyssey can last years and usually there are multiple misdiagnoses along the way. If we don’t know what disease we are dealing with we can’t be sure we are providing the best care. A NBS for MLD, even without a treatment, would avoid the diagnostic odyssey and allow parents to know up front what to anticipate for the best care of their child – resulting in an optimized quality of life for their child and for the family.

There are good arguments for requiring a viable treatment before formalizing a NBS as well. Test and treat – don’t create a sense of helplessness and panic where there is no therapy. Don’t cause parents to take desperate actions to “do anything” for their child.

In the absence of a viable treatment a whole slew of questions come to mind … who is going to follow up with and provide social and medical care for the family, is there a financial impact on society for increased earlier care, would the role of the family support organizations change, what about the ethics of detecting a disease with a later onset, or parents that want to opt out except for disease with viable therapies, etc. …

Parents and families are starting to clamor for more medical knowledge sooner so they can better care for their children and industry is also awakening to the advantages of a pre-viable-therapy NBS – the potential negative this would have on the ability to capture natural histories that are necessary to get therapies approved being traded off for the identification of patients for potential study and real disease prevalence information.

I am calling for a NBS Therapy Summit or series of summits in the near future, perhaps starting next fall or winter, to encourage all interested and affected parties to share their concerns, views, issues, and thoughts. An open discussion will give us all indications as to if the viable therapy requirement should be reconsidered. If you are a public health official, researcher, policy/regulatory person, SACHDNC committee member, parent, advocacy group member, an industry representative, clinician, or just interested in this topic I encourage your participation.

Follow this blog and I will keep you posted on any progress towards a summit..

I was pleased to be the organizer and host for the RARE Project | Global GenesRARE Patient Advocacy Summit on September 29th, 2012. The day-long event with 140 in attendance and over 120 viewing via a live webcast. Videos of the event are available below for viewing. Continue reading →